ECTODERMAL DYSPLASIA

1. Dr. Yugandar

2.  ectodermal dysplasias is of a group of inherited disorders
that share in common developmental abnormalities of two
or more of the following: hair, teeth, nails, sweat glands and
other ectodermal structures like
 mammary gland, thyroid gland, thymus, anterior
pituitary, adrenal medulla, central nervous system, external
ear,melanocytes, cornea, conjunctiva, lacrimal gland and
lacrimal duct.

3.  One definite benefit is that the problems encountered
by many patients and families are grouped regardless
of the specific subtype of ED &
 Parents and children can benefit by being part of larger
support networks exemplified by the Ectodermal
Dysplasia Society
http://www.ectodermaldysplasia.org
the National Foundation for Ectodermal Dysplasias
http://www.nfed.org

4.  Many conditions encompassed by this broad
definition are not usually considered as primarily ED
 incontinentia pigmenti,
 dyskeratosis congenita,
trichothiodystrophies,
Cardio facio cutaneous syndrome,
pachyonychia congenita & Goltz syndrome
 By Definition they are ED, but
common practice has been to consider many of these as
separate entities

5.  The first clinical cases with features of ED were reported as
early as 1792, when Danz described two Jewish boys with
congenital absence of hair and teeth
 In 1875 Charles Darwin reported the case communicated to
him by a Mr. Wedderburn,
 Hindoo family in Scinde in which ten men, in the course of
four generations, in their both jaws taken together, with only
four small and weak incisor teeth and with eight posterior
molars
 This family would have X-linked hypohidrotic ectodermal
dysplasia

6.  small series of cases with hypotrichosis, hypodontia,
onychodysplasia and anhidrosis
had been described under various names such as
 dystrophy of hair and nails
 imperfect development of skin, hair and teeth
 congenital ectodermal defect
 term ‘ectodermal dysplasia’ appear 1929
 Touraine suggested ‘ectodermal polydysplasia’

7. Weech specified three essential aspects of ectodermal
dysplasias:
 most of the disturbances must affect tissues of
ectodermal origin
 these disturbances must be developmental
 heredity plays a causal role

8.  Ectoderm is one of the three primary germ cell layers in the
very early embryo
 The other two layers are the mesoderm (middle layer) and
endoderm , with the ectoderm as the most exterior layer
 It emerges and originates from the outer layer of germ cells
 The word ectoderm comes from the Greek ektos meaning
"outside", and derma, meaning "skin."

9.  Ectoderm differentiates to form
 the nervous system (spine, peripheral nerves and brain),
 tooth enamel and the epidermis
 It also forms the lining of mouth, anus, nostrils, sweat
glands, hair and nails
 In vertebrates, the ectoderm has three parts: external
ectoderm (also known as surface ectoderm), the neural
crest, and neural tube
 the latter two are known as neuroectoderm

11.  1.Pre aortic ganglion
 2.Sympathetic
ganglion
 3.Organ plexus
 4.Suprarenal gland
 5.Dorsal root ganglion
 6.Surface ectoderm
 7.Neural tube
 8.Dorsal aorta
 9.Urogenital ridge
 10.Notochord

12.  mutation or deletion of certain genes located on different
chromosomes.
 ED s are caused by a genetic defect they may be inherited
or passed on down the family line.
 In some cases, they can occur in people without a family
history of the condition, in which case a de novo mutation
has occurred.

13.  Connexin defects :
 Gap junctions are intercellular channels that connect the
cytoplasm of neighbouring cells,
 Facilitating cellular growth, differentiation,tissue
morphogenesis, homeostasis
 Transmembrane connexin proteins undergo
oligomerization to form the connexons that compose Gap
junctions

14.  In the Golgi network
six connexin subunits assemble
to form a connexon
 The connexon is then
transported to the plasma
membrane.
 Other connexons then
coaggregate to form
homotypic or heterotypic gap
junctions.

15.  Cx26, Cx30, Cx31 and Cx43 expressed in ectoderm-
derived epithelia of the inner ear and cornea as well as in
the epidermis and its appendages
 Connexin defects a/f the sensorineural deafness, keratitis
and cutaneous abnormalities (ranging from keratoderma
to erythro keratoderma to ectodermal dysplasias
affecting the hair and nails)

16.  Are the ectodermal dysplasias hereditary?
 The ED are caused by alterations in genes
 Altered genes may be inherited from a parent
 Normal genes may become altered (mutate) at the time of
egg or sperm formation or after fertilization
 Chances for parents to have affected children depend on the
inheritance pattern of the type of ectodermal dysplasia

17. New Mutation:
 Generally, when a mutation has occurred, there is little chance
that it will occur in another child of the same parents
 The affected child may transmit the trait

18.  Autosomal Dominant :
 When the ED is an autosomal dominant trait, the parent
who is affected has a single copy of the abnormal gene
and may pass it on to his or her children
 Regardless of the gender of the parent or the child,
there is a 50% chance for each child
 All children who receive the abnormal gene will be
affected

20.  Autosomal Recessive
 When the ectodermal dysplasia in the family is an autosomal
recessive trait, the usual situation is that each parent is unaffected
 The parents are said to be carriers
 They each have a single copy of the abnormal gene
 the chance for them to have another affected child is 1 in 4
 1 in 4 children get a copy of the abnormal gene from each
parent and is affected
 2 in 4 gets only one copy each and are carriers
 the remaining 1 in 4 inherits a normal gene from each parent
and is not affected

22.  X-Linked Recessive
 If a woman is a carrier of an X-linked recessive
disorder
 there is a 50% chance that each male child will
receive the abnormal gene and be affected
 50% chance that each female will receive the
abnormal gene and be a carrier (like the mother).
 If a man has the abnormal gene
 he is affected and will pass the gene on to all of his
daughters. The daughters will be carriers
 Since the gene is on the X chromosome, sons will
not be affected because they receive the mans Y
chromosome

24.  Freire-Maia and Pinheiro classification depend on clinical
phenotypes
& inheritance patterns of ED
 designated conditions by groups depending on presence
of hair, nail, tooth or sweat gland abnormalities
 conditions that had involvement of
hair (1), teeth (2), nails (3) ,sweat glands (4),other
ectodermal (5)

25.  Classification: molecular approaches
Plays important insights into the molecular basis of
the ED
 the molecular data have confirmed clinical
impressions,
Eg: Hay–Wells syndrome and
ectrodactyly, ectodermal dysplasia,
clefting (EEC) syndrome

26.  Classification: Genetic mechanisms
 ED due to mutations in tumour necrosis factor
(TNF)-like/NF-κB signalling pathways,
the p63-related ED
 ED due to other transcription factors
 ED due to mutations in gap junction proteins.

27.  In an attempt to classify these, different subgroups are
created according to the presence or absence of 4
primary ED defects:
 ED1: Trichodysplasia (hair dysplasia)
 ED2: Dental dysplasia
 ED3: Onychodysplasia (nail dysplasia)
 ED4: Dyshidrosis (sweat gland dysplasia)

28.  Eds are categorised into one of the following subgroups
made up from the primary ED defects
 Subgroup 1-2-3-4
 Subgroup 1-2-3
 Subgroup 1-2-4
 Subgroup 1-2
 Subgroup 1-3
 Subgroup 1-4
 Subgroup 2-3-4
 Subgroup 2-3
 Subgroup 2-4
 Subgroup 3
 Subgroup 4

29.  In 2001, Priolo and Laganà reclassified the ectodermal
dysplasias into 2 main functional groups:
 (1) defects in developmental regulation/epithelial-
mesenchymal interaction
 (2) defects in cytoskeleton maintenance and cell stability.

30.  In 2003, Lamartine reclassified ED into the following 4
functional groups based on the underlying pathophysiologic
defect:
 (1) cell-to-cell communication and signaling
 (2) adhesion
 (3) development
 (4) other

31.  The most common ectodermal dysplasias
 Hypohidrotic ED which falls under subgroup 1-2-3-4
 Hidrotic ED which comes under subgroup 1-2-3.

32.  The three most recognised ED syndromes fall into the
subgroup 1-2-3-4
 they show features from all four of the primary ED
defects
 Ectrodactyly-ED-clefting syndrome
 Rapp-Hodgkin hypohidrotic ED
 Ankyloblepharon, ectodermal defects, cleft lip/palate
(AEC) or Hay-Wells syndrome

33.  X-linked HED is the most common of ED
 Charles Darwin described it first,Later by Christ,
Siemens & Touraine
 characterized by
o hypotrichosis
o hypodontia,
o hypohidrosis

34.  Majority are X-L-R inheritance
 involved gene ED- 1,located on Ch X-q12-13.1.
 Encodes a protien ECTODYSPLASIN A ,member of
TNF family

35.  AD & AR inheritance can occur
 Autosomal gene has been mapped to Ch 2q 11-q1
(ED 3 )
 CRINKLED gene identified – AR HED
 Autosomal recessive HED is clinically identical to
X-linked HED
 females are as severely affected as males

36. PATHOPHYSILOGY :
 Mutations in the EDA, EDAR, and EDARADD genes
cause HED
 The EDA, EDAR & EDARADD genes provide
instructions for making proteins
 These proteins form part of a signaling pathway that is
critical for the interaction between two cell layers, the
ectoderm and the mesoderm

37.  Hair:
 Scalp hair is sparse, fine, lightly pigmented and grows
slowly
 Eyebrows & eyelashes are scanty or absent
 Secondary sexual hair in the beard, pubic and
axillary regions is variably present and may be normal
 Hair on the torso and extremities is usually absent

39. Teeth:
 Both deciduous and permanent teeth are affected
 The alveolar ridges are hypoplastic
 missing teeth or retarded growth of teeth
 peg-shaped
 Tooth enamel is also defective
 Dental treatment is necessary & children as young as 2
years may need dentures

40. Conical teeth

41. • Upper Incisors have been resorted
• Orthopantogram shows absence of 10 Primary & 11
Permanent teeth

43.  Nails : Nails are normal in most individuals
 Sweat glands:
 Sweating is severely diminished or absent due to a
paucity or absence of eccrine glands
 An absence of sweating leads to an inability to
thermoregulate

44.  Thermoregulation is most problematic in infants and
young children, may recurrent bouts of fever as high as
42°C
 Heat intolerance can occur in older children and adults

45.  Skin:
 At birth, affected males may demonstrate marked
scaling or peeling of their skin
 skin is fine, smooth and dry in adults
 Peri orbital hyperpigmentation
 fine wrinkling around the eyes

46.  Eczema is common and is prominent in flexural areas
 Small milia like papules may be found on the face
 Diminished or absent salivary
glands & mucous glands of the nose, mouth and ears cause
 nasal obstruction by thick, fetid nasal discharge &
adherent nasal crusts, sinusitis
 recurrent upper respiratory tract infections

47.  Diminished production of tear film
from the lacrimal glands cause dry eyes, photophobia &
corneal damage
 affected males have abnormalities of the nipples
including absent, simple or accessory nipples
 feeding problems in infancy
 xerostomia,hoarse voice & impacted cerumen

48.  Craniofacial features:
 Distinctive facies with frontal bossing, concave midface,
saddle nose and everted lips
 30% of affected males have small ears
 facial features may not be obvious at birth, but become
more noticeable with age

50.  HistoPathology:
 The epidermis is thin with effacement of rete ridges.
 Hair follicles and sebaceous glands, Apocrine glands are
variably reduced
 Mucous glands of the upper respiratory tract may be sparse

51.  Light and scanning electron microscope findings of
hair shaft abnormalities are longitudinal clefts or
grooves and transverse fissuring,bulb of the hair
shaft is dystrophic
 Mandible X-ray show Dental hypoplasia or aplasia

52.  Epidermal & follicular orthokeratotic
hyperkeratosis
 Arrector Pili muscle oriented parallel to skin surface
 Apocrine ducts enter follicles at abnormal locations
 Comedo formation

53.  Prognosis:
 Failure to thrive occurs in up to 40% of affected males
 Height and weight are compromised in early childhood but
appear to normalize with time.
 Mortality in infancy and early childhood is historically 25%
 Due to hyper thermia, failure to thrive and respiratory
infections

54.  Associated Hyperthermia desreves in early diagnosis in
childhood
 Careful clinical examination
 Standard methods for Sweat production & Sweat pore
counts by Silicone rubber plastic imprints,Starch – Iodine
test,Pilocarpine iontophoresis,Valerio Ventruto Tech
( Palmar finger tip Sweat pore counting )

55. Skin biopsy :
 absence or sparse sweat glands in dermis of hypothenar
area
 decrease no of sebaceous glands & hair follicles in other
areas

56. Mortality/Morbidity:
 related to the absence or dysfunction of eccrine and
mucous glands.
 Intermittent hyperpyrexia may occur in infants with
decreased sweating.
 The mortality rate approaches 30%. Recurrent high
fever may also lead to seizures and neurological
sequelae

57.  Pharyngitis, rhinitis, cheilitis
 dysphagia may result from reduced numbers of
functional mucous glands in the respiratory and
gastrointestinal tracts.
 Growth failure is common.

58.  No specific treatment for ectodermal dysplasia
 Management of ED is by treating the various symptoms
 Patients often need to be treated by a team of doctors and
dentists, rather than a sole practitioner
 abnormal or no sweat gland function should live in cooler
climates or in places with air conditioning at home, school
and work.

59.  Artificial tears can be used to prevent damage to the
cornea in patients with defective tear production
 Saline irrigation of the nasal mucosa may help to
remove purulent debris and prevent infection
 Early dental evaluation and intervention is essential

60.  Surgical procedures such as repairing a cleft palate may
lessen facial deformities and improve speech.
 Research on Gene correction or administration of
recombinant EDA protein. Proof of principle has been
achieved in a dog model for this approach

61.  Psychological support for affected children
 Prevention :
 Prenatal Diagnosis by fetal skin biopsy possible after 24
weeks of gestation ( Sweat gland start to develop )
 Glands may be shriveled or absent
 DNA probing tech on Chorionic Villus Biopsy

62.  infants with scaling skin may be misdiagnosed as
collodion babies with lamellar ichthyosis
 Basan syndrome is characterized by
hypotrichosis, hypodontia and hypohidrosis, but also by
severe nail dystrophy and congenital absence of
dermatoglyphics

63. Differential Diagnosis:
 Alopecia Areata
 Aplasia Cutis
 Congenita Focal Dermal Hypoplasia Syndrome
 Incontinentia Pigmenti
 Naegeli- Franceschetti-Jadassohn Syndrome
 Pachyonychia Congenita

64.  Palmoplantar keratoderma
 Hypotrichosis
 Nail dystrophy
Genetics :
 AD pattern,ED 2,
 Ch 13q11-q12.1,member of Gap jn family connexin- 30

65. Clinical features :
 Nail dystrophy –MC,short discolored, thickened
with striations are seen over bulbous finger tips

66.  Scalp hair: thin,brittle,normal at birth gradually hair loss &
total alopecia
 Axillary & Pubic hair are vellus or sparse or absent
 Diffuse palmoplantar keratoderma with deep fissuring
 Sweating is normal

67.  Skin thickening beneath free edges of nails,finger
joints,knuckles
 Thickening of skull bones,tufting of terminal
phalanges of fingers and nails
 Oral leukoplakia may be seen
 Teeth may be normal,prone to Early Caries

68.  Syndactylyl & Polydactylyl
 Mental & Physical Retardation

69.  Diagnosis :
 Palmoplantar Keratoderma
 normal facies, normal sweating & teeth differentiate .
 Prognosis:
 Life expectancy will be normal
 Persistent Malodourous Onychomycosis
 Squamous cell carcinoma of nail bed

70.  Management:
 Keratolytic agents & Emollients for PPK
 Systemic Retinoids

71.  Very Rare, Both Mesodermal & Ectodermal structures
 Described by COCKAYNE in 1936
 3 types:
 EEC 1,
 EEC 2,
 EEC 3

72.  GENETICS :
 AD pattern
 Mutation of P 63 gene ( similar to P53) located on Ch
7q11.2-q21.3
 P63 is critical to maintain Progenitor cells responsible
for Genesis of Limbs & Cranio facial regions in fetal
life

73.  Clinical features:
 Lobster claw deformity: Split hand & foot – MC
 3rd & 4th Digits - MC
 Tetramelic involvement –MC
 Nails Hypoplastic & Dystrophic
 Cleft Palate & Lip

75.  Typical face : Hypoplastic Maxillae, Short
Philtrum, Broad Nasal tip
 Oligodontia & Anodontia
 Hair: Sparse,dry,scalp dermatitis
 MR, hamartoma of tongue, hydronephrosis

76. MAJOR MINOR
 ED
 Ectodactyly
 Cleft Palate/Lip
 Lacrimal duct abnor.
 Renal Anomolies
 Deafness
 MR
 Choanal atresis
X – Ray of deformed hand show absence or
hypoplasia of Meta carpals & Metatarsals

77.  Prognosis :
 Corneal Scarring & Blindness due to Recurrent Keratitis
 Treatment :
 Repair of Cleft palate & Lip
 Multi disciplinary approach for other abnormalities
 Prevention :
Cleft Lip/Palate – Prenatally by USG

78.  Genetics :
 AD Pattern
 Missense Mutation in SAM domain of P63

79.  cleft lip/palate
 hypotrichosis, hypodontia,
 absent or dystrophic nails ,mild hypohidrosis
 One distinctive feature is ankylo blepharon filiforme
adnatum—partial thickness fusion of the eyelid margins

80.  severe scalp erosions
 Scalp dermatitis with erosions may result in
scarring alopecia

81.  CLINICAL FEATURES :
 Babies at birth have Erythroderma – MC
Peeling, red, parchment-like
skin in a newborn parchment skin resolves over the first few
weeks of life and the underlying skin is dry

82.  Marked hypohidrosis – heat intolerance
 Hair is sparse, pale with STEEL WOOL Texture
 Hair shaft abnormalities – PILI TORTI
 Nail dystrophy, Cleft palate /Lip

83. • Abnormal hair shaft showing PILI TORTI &
Longitudinal groove ( PILI CANALICULI )

84. Hands of son and father showing brittle,thin
& dystrophic nails

85.  Face : Frontal bossing ,maxillary hyperplasia
 narrow nose, broad nasal bridge & small mouth
 Fusion of EYE LIDS most distinc feature
 Hypodontia or Conical Teeth

86.  VSD
 Syndactylyl,
 Treatement :
 Surgical correction of eye lids
 Correction of Hyperhidrosis

87.  AR inheritance
 Cong. Membranous aplasia cutis of scalp
 Deafness,Dwarfism
 MR,Hypotonia
 Genital abnormalities
 DM,Hypothyroidism

88.  AR inheritance
 Cysts at eyelid margins
 Palmo plantar keratoderma
 Hypotrichosis
 Hypodontia
 Benign & Malignant tumors of Palms & Soles

89.  Berlin syndrome : Generalized grayish-brown
hyperpigmentation with Sparse eyebrows with absent
lateral aspect, delayed dentition/hypodontia, short
stature, sexual underdevelopment in male patients,
mental retardation
 Described in one family (Iranians living in Israel; four
affected siblings; consanguineous parents)

90.  Lucky/Winter syndrome
 Generalized hyperpigmentation with guttate
 Scant lightly pigmented hair, enamel hypoplasia (single
central incisor in one patient), Likely autosomal dominant
inheritance

91.  Acromelanosis albo-punctata syndrome
 Diffuse hyperpigmentation with atrophic skin guttate on
the dorsal aspects of the hands and feet
 Keratotic follicular papules on the legs
 pili torti
 platonychia

92. Nails Hair Teeth Sweat gland others
HYPO
HIDROT
IC ED
Gen
Normal
Dry,hypochromic &
hypotrichosis of scalp
Moustache & Beard -
Normal
Eye brow & Lashes -
absent
Hypodontia
Peg shaped
incisors /
canines
Dec Epidermal
ridge sweat
pores
Skin –thin,dry - abs
sebaceous gl
Face: Saddle
nose,frontal bossing
Pharyngitis
Laryngitis
Aplasia of Breast
HIDROT
IC ED
Thickened/
discoloure
d,
clubbing
Dry,Slow Growing, Eye
brow/ Lashes- Scanty
or abs
Occ
Anodontia/
hypodontia,
caries
Normal Skin-Dry,scaly
Thick dyskeratotic palms
& soles
Tufting of terminal
Phalanges,myopia
EEC ED Thin,
pitted,
striated
nails
Hypotrichosis of
scalp,body
Eye brow/Lashes - abs
Ano/hypo/mic
ro dontia
Occasionally
hypohidrosis
without
hyperthermia
Palmoplantar
hyperkeratosis,cleft
lip/palat,speckled
iris,syndactylyl,ectrodatyly
l,clinodactylyl,
AEC Sever
dystrophy
Hypotrichosis
Steel wool texture
PILI TORTI
PILI CANALICULI
Sever
hypodontia
Hypohidrosis but
no hyperthermia
Dry smooth,pp
hyperkeratosis,dermatogl
yphic patter- abs,Scalp
pustulation

93. No / Severely reduced
sweating
Sev Immune
defect
• HED/IM
No Immune eff.
• X-LR HED
• AD- HED
• AR-HED
Normal/mild dec sweating
Normal teeth
• Clouston
• ED/skin
fragility
Abnormal
teeth
No
facial
cleft
• Tooth &
nail
/witkop
•
Trichodent
oosseous
Facial cleft
Limb abnormality +
• EEC
• Margarita island ED
• Limb-mammary
Limb abnormality –
• AEC
• Rapp- Hodgkin ED

94.  One well known person with ED is Actor
Michael Berrymen

95.  Famous Skate boarder & artist Levi
Hawken,well known with Nek Minit Videos on
you tube

96. Thank You Very Much

97. Thank you